There are numerous methods for identifying and probing genomic markers in tumor cells, most of which are based on nucleic acid amplification technologies. However, in many instances protein markers are going to be of even greater utility in identifying and classifying tumor cells than genetic markers. To this end, it would be extremely useful to have methods by which protein (rather than nucleic acid) markers could be amplified. In this proposal we outline a series of novel methods for transducing tumor cell antigens to amplicons, which can in turn be sensitively detected using methods common to nucleic acid diagnostics. In particular, it has previously been shown that nucleic acid binding species (aptamers) selected from random sequence pools can specifically interact with a wide range of protein targets, including those relevant to tumor biology. Aptamers typically bind their cognate targets with dissociation constants in the nanomolar range and can readily discriminate between even closely related proteins. For these reasons, aptamers should prove useful for recognizing a wide range of protein markers associated with cellular transformation. We have previously developed automated methods for the selection of aptamers. We now propose to use such automated methods to target cell surface antigens of tumor cells. Selected anti-tumor aptamers will be adapted to a number of important diagnostic methods, including methods to label tumor cells and methods to transduce tumor protein antigens into nucleic acid amplification assays, via two novel methods, proximity ligation assays and rolling circle amplification.